The Center for Narcolepsy and Related Disorders is a multidisciplinary research program on the etiology, diagnosis, prevention and treatment of these debilitating and poorly understood sleep pathologies. The disorders have clinical manifestations including excessive daytime sleepiness, recurring bouts of flaccid paralysis of the postural (anti-gravity) musculature (cataplexy), sleep-onset periods of rapid-eye-movement (REM) sleep (short REM latency),vivid (hypnagogic) hallucinations, and sleep paralysis. Current estimates indicate that narcolepsy afflicts more than 250,000 people in the United States, and with the related disorders, represents a significant public health problem. A multidisciplinary approach to research on these diseases is required because of the prime involvement of diverse biological systems including the central nervous and immune systems and the genome. We have brought together the critical mass of specialists in the necessary fields to advance knowledge in the area and build on the significant progress made during the last three years. The proposed work is divided into eight different but inter-related scientific projects: Project B - Pharmicology of Narcolepsy, Project C - Neurotransmitter Mechanisms in Canine Narcolepsy, Project D - Receptor Mechanisms in Narcolepsy, Project E - Neuroptiysiology of Canine Narcolepsy: Pontine and Amygdala Unit Activity, Project F - Thermoregulation in Canine Narcolepsy, Project G - Immunogenctics and Neuroimmunology, Project H - Linkage Markers in Narcolepsy, and Project I - Human Twin Studies. They include research on the only available animal model which provides a unique opportunity to study the fundamental neurochemical mechanisms involved in these diseases, and to quickly test new strategies for treatment that emerge as a result of these investigations. The growing realization of the enormous personal and societal consequences resulting directly or indirectly from sleep pathologies mandate a continued investment into research in these diseases.